Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Breast cancer is the commonest killing malignant disease of women in the European Community. The average annual age standardised mortality rate among the 12 EEC countries ranges from 28.5 to 13.7 per 100,000 females. In Ireland, breast cancer is treated primarily by general surgeons. At our Breast Institute at St. Vincent's Hospital where we see 100 patients with breast diseases weekly it is policy to recommend quadrantectomy, total axillary dissection and radiotherapy (QU.A.R.T.) for patients with T1 and T2 tumours if they are peripherally placed within the breast. Complete axillary dissection in early breast cancer provides accurate staging and virtually eliminates axillary recurrence and the dissection is standardised and audited in our unit. Audit of axillary dissection improves the lymph node yield and enhances the completeness of the procedure. Sophisticated mammography improves the detection of small tumours but even excellent mammography may fail to identify malignant disease. Screening programmes for early breast cancer detection should be based on clinical examination in addition to mammography and some 15% of our patients with palpable breast cancer had falsely negative mammograms. Before operation, extensive scintigraphy and sonography is carried out before primary treatment is undertaken. After treatment, clinical and biochemical surveillance is carried out. We have found the lysosomal protease, Cathepsin D to be a useful marker of progressive disease and prognosis in patients with breast cancer. Routine postoperative CEA and CA15.3 are also valuable markers and a high or rising CA15.3 often precedes clinical or investigative evidence of recurrence. In addition, assay of c-erB-2 protein by ELISA is also a simple, rapid quantitative prognostic guide in patients with breast cancer.
 ...
PMID:Aspects of breast cancers. 134 Dec 88

17 beta-Estradiol stimulates the secretion of the 34- and 52-kDa protein (i.e., cathepsin D and procathepsin D, respectively) from MCF-7 human breast cancer cells and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) inhibits this estrogen-stimulated response. A comparison of the effects of 17 beta-estradiol, TCDD, and their combinations on the secretion of these two proteins was determined using four different assay procedures, namely autoradiographic analysis of the 35S-labeled proteins (from [35S]methionine) separated by polyacrylamide gel electrophoresis (PAGE), densitometric analysis of the silver- and double-stained proteins separated by PAGE, and radioimmunoassay of the proteins using commercially available antibodies to the 52-kDa protein. The results showed that the autoradiographic, staining, and radioimmunoassay procedures gave comparable results with only a few minor differences in the relative amounts of the 52-kDa detected in the various treatment groups. In the medium obtained from 17 beta-estradiol-treated cells that was serially diluted, there was an excellent linear correlation for the relative concentrations of the 52-kDa protein using the double-staining/densitometric procedure and the radioimmunoassay. These results indicate that the double- or silver-staining method may be a useful and rapid method for screening new compounds as antiestrogens in MCF-7 cells.
 ...
PMID:Development of gel staining techniques for detecting the secretion of procathepsin D (52-kDa protein) in MCF-7 human breast cancer cells. 138 Nov 55

A number of growth factors have been implicated in the control of the proliferation of breast cancer cells and some have been reported to mediate the proliferative effects of oestradiol. MCF-7 cells were treated with growth factors in the presence and absence of oestradiol. Oestradiol increased the response of cells to the proliferative effects of epidermal growth factor (EGF), transforming growth factor alpha (TGF-alpha) and basic fibroblast growth factor (bFGF). Platelet derived growth factor (PDGF) and cathepsin D had no effect in the presence or absence of oestradiol while TGF-beta slightly reduced the stimulation by oestradiol. In the absence of oestradiol, there was little effect of combinations of growth factors although the effects of bFGF and IGF-I were additive. In the presence of oestradiol, the effects of bFGF and TGF-alpha were additive whereas bFGF acted as an IGF-I antagonist. Overall, bFGF had the greatest effect on cell proliferation although this was less marked than the previously described effect of the IGFs and insulin. The effects of oestradiol on the sensitivity of cells to the proliferative effects of bFGF did not appear to result from regulation of bFGF receptor expression.
 ...
PMID:Modulation of the proliferative response of breast cancer cells to growth factors by oestrogen. 141

Since 1982 we have been evaluating oestrogen and progesterone receptors (PgR), cathepsin D and the cytosolic levels of the tumour marker, tissue polypeptide antigen (TPA), in 257 patients radically resected for breast cancer (follow-up 24-81 months). TPA was measured by an immunoradiometric assay previously validated for cytosol. No significant associations were found between cytosolic TPA and age, tumour size, lymph-node status, receptor status and cathepsin D. TPA+ cases showed a significantly longer disease-free survival (DFS) and overall survival (OS) than TPA-patients (log-rank P < 0.0001). The prognostic value of cytosolic TPA was also demonstrated after stratification by nodal status, PgR and cathepsin D. The prognostic value of TPA was independent of the other prognostic indicators, being the most powerful among the evaluated indices (Cox multivariate analysis: chi 2 15.5 for DFS, 11.4 for OS). We conclude that cytosolic TPA is a powerful additional prognostic factor in primary breast cancer. Its prognostic role should therefore be extensively evaluated.
 ...
PMID:Tissue polypeptide antigen in breast cancer cytosol: a new effective prognostic indicator. 144 48

Data were obtained on soluble oestrogen (ER) and progesterone (PR) receptors from 273 primary breast tumours, using an enzyme immunoassay (EIA) and ligand binding assay with dextran-coated charcoal (DCC) or isoelectric focussing separations. The p29 and total cathepsin D content was also assayed in the same samples. Tumours expressing ER (by either steroid binding assay or EIA) had higher levels of p29 than those which did not express the receptor (P < 0.0001). Moreover, tumours co-expressing ER, PR and p29 appeared to have higher levels of cathepsin D than those which were negative for at least one protein (P < 0.0001). Twenty out of the 273 human breast cancer samples, containing a level of ER positive by EIA, which did not bind labelled oestradiol, were identified; isoelectric focussing showed that such a receptor was also unable to bind hydroxytamoxifen. These tumours did not significantly differ from those in the whole population in their capacity to express ER (positive by EIA), PR, p29 and cathepsin D. It was concluded that the EIA can detect both a ligand binding ER and a receptor which is able to initiate PR transcription but does not bind radio-labelled ligands in vitro; such a receptor could have a bearing on the variability of tumour response to endocrine therapy.
 ...
PMID:Transcriptionally active non-ligand binding oestrogen receptors in breast cancer. 145 Nov

Ovarian cancers are highly invasive. In a first attempt to define the hormones and factors involved in the control of tumor invasion and metastasis, we have used the human ovarian cancer cell line BG-1 which contains both estrogen and progesterone receptors. Protein synthesis and secretion was assayed by [35S]methionine incorporation and polyacrylamide gel electrophoresis followed by fluorography. Three responses to estradiol were found: 1) procathepsin D secretion was increased, whereas the corresponding intracellular proteins were not significantly affected; 2) an abundant but nonidentified 120-kilodalton (kDa) estrogen-induced secreted glycoprotein, different from CA125, was detected for the first time; and 3) the number of cells as determined by DNA assay was markedly stimulated, reaching a higher level of confluency. The antiestrogen OH-tamoxifen was weakly agonist at low concentrations to stimulate cell growth but was a pure antagonist on the 120-kDa protein. The steroid specificity of these responses strongly suggests that they are mediated by the estrogen receptor. We conclude that cathepsin D secretion is specifically stimulated by estrogen in this ovarian cancer cell line as it is in estrogen receptor-positive breast cancer cells. Both cathepsin D and a newly described 120-kDa secreted glycoprotein are potential markers of hormone responsiveness and/or aggressiveness which deserve to be further studied in clinical ovarian cancers.
 ...
PMID:Estradiol stimulates cell growth and secretion of procathepsin D and a 120-kilodalton protein in the human ovarian cancer cell line BG-1. 146 54

Forty patients with intermediate stage (T2 > 3 cm-T3, N0-N1) operable breast cancer received neoadjuvant chemotherapy by MCF (mitoxantrone, cyclophosphamide, 5-fluorouracil). Four cycles were administered at 3-week intervals. The obvious hematological toxicity (64% of grade III for the leucocytes and up to 34% of grade IV for the granulocytes) was rapidly reversible and did not hinder completion of the treatment. Ten patients showed a complete remission and a tumor volume regression of more than 50% was observed in 12 other patients. Tumor shrinkage allowed breast-saving surgery in 50% of the cases. A complete sterilisation of the surgical specimen was found in only two of the 40 patients and a few persisting neoplastic cells were found in ten other cases. A positive response at the level of the axillary lymph nodes was also obtained in more than 50% of the cases. In 25 of the 36 cases examined, the primary chemotherapy induced cellular lesions (fibrosis, necrosis) at the tumor level. A feasibility study was undertaken in order to determine quantitatively several biochemical parameters (steroid hormone receptors, cathepsin D, c-erbB-2 oncoprotein) in very small tumor samples obtained by Tru-Cut before any treatment and in surgical specimens. In the future, these micromethods will be used systematically with the aim of estimating the value of these potential prognostic factors for therapeutic follow-up of the patients.
 ...
PMID:[Neoadjuvant chemotherapy, with mitoxantrone, cyclophosphamide and fluorouracil, in operable breast cancer of intermediate stage: first results of a phase II study in 40 patients]. 148 24

To determine overexpression of cathepsin D in head and neck tumours we examined cytosols from 53 primary tumours, nine cytosols of lymph node metastases and 12 cytosols from adjacent normal tissue. We found a significantly lower concentration in normal tissue compared with tumour cytosol as well as with metastases, even when we compared tumours and corresponding metastases pairwise. In addition, we found a significantly higher concentration of cathepsin D in five lymph node metastases than in the corresponding tumours. We conclude that the reported role of cathepsin D is not restricted to breast cancer but could also be important in head and neck cancer.
 ...
PMID:Expression of cathepsin D in head and neck cancer. 151 61

Cyst fluids from 55 premenopausal women with gross cystic breast disease were classified by K+/Na+ ratio: 19 with ratio over 1 (type I) and 36 with ratio less than 1 (type II). Immunoradiometric assay of cathepsin D in both types of cyst fluids revealed the presence of large amounts of this proteinase. The average concentration of cathepsin D in type I cyst fluids was 63.3 nmol/l, which was significantly higher than that corresponding to type II cyst fluids (35.1 nmol/l). Immunoprecipitation analysis of intracystic cathepsin D demonstrated that this protein was present as the 52 kD non-processed precursor form of the molecule. Since procathepsin D is a useful prognostic marker in breast carcinoma, we suggest that cyst fluid quantification of cathepsin D could aid to detect patients affecting of gross cystic disease with higher risk for developing breast cancer.
 ...
PMID:Quantification and molecular analysis of cathepsin D in breast cyst fluids. 152 2

About 8% of women in Norway will develop breast cancer. 55% of these will have a node negative disease. The current debate concerns whether all women in stage I should be treated with adjuvant therapies. In this article we discuss different prognostic factors with the objective of subdividing node negative breast cancer patients into different prognostic groups. Risk factors include age under 30 years and over 70 years, increasing size of tumour, a high histological grade and negative oestrogen receptor status. We believe that, in future, evaluation of ploidy, proliferation antigens, oncogenes and possibly cathepsin D will be useful in selecting breast cancer patients in stage I for adjuvant therapy.
 ...
PMID:[Prognostic parameters in localized breast cancer]. 156 96


1 2 3 4 5 6 7 8 9 10 Next >>